Abstract

OBJECTIVES To assess the frequency and severity of coughing and choking episodes, possible related factors, and their association with
chest infections in patients with motor neuron disease (MND).

METHODS Thirty seven patients with MND and 23 healthy volunteers were studied. Cough was assessed using a questionnaire and a 3 day
diary, and volitional cough quantified by peak cough flow and sound intensity. Other clinical symptoms, smoking habit, affective
state, oral secretions, bulbar signs, and quantitative assessments of swallowing and respiratory function were documented.

RESULTS Patients with MND coughed and choked significantly more often and to a greater degree than the healthy volunteers (26 of
37 patients with MND and 2 of 23 volunteers, p<0.001). Female sex, older age, abnormal speech, reduced swallowing capacity,
and low forced vital capacity (FVC)% predicted were each significantly associated with excessive coughing and choking episodes
in patients with MND. Smokers had significantly more severe and prolonged episodes of coughing and choking than non-smokers
(p<0.05). Patients with upper motor neuron bulbar signs had a greater tendency to severe and prolonged episodes of coughing
and choking than those without (p<0.05). Chest infections were reported only rarely among the patients who coughed and choked.

CONCLUSIONS Coughing and choking episodes are common in patients with MND but infrequently associated with overt chest infection. Upper
motor neuron bulbar signs may both promote factors (for instance, dysphagia) which trigger cough and reduce volitional capacity
to suppress it.

There is no curative treatment available currently for motor neuron disease (MND), and the palliation of symptoms of the disease
is of paramount importance.1 One of the most distressing of these symptoms commonly reported by patients is coughing and choking. In normal people cough
is a distinct phenomenon from choking (the feeling of suffocation or blockage of breathing) but in patients with MND they
are difficult to differentiate. There is little information in the literature about the frequency and cause of coughing and
choking episodes in patients with MND,2 and in particular, whether such symptoms presage an imminent chest infection. The purpose of this study was to assess the
severity of these events, to detail related factors, and to clarify how often such patients developed chest infections. Preliminary
data were presented previously at a meeting of the Association of British Neurologists'.3

Methods

PATIENTS

Patients with MND (diagnosed according to the El Escorial criteria)4 were recruited from the neurology ward, the general neurology clinics at University Hospital of Wales, and the MND clinic
at Rookwood Hospital. Healthy volunteers without a history of swallowing, breathing, or neurological disorder were recruited
from hospital staff and the general public.

TECHNIQUES

Patients kept a 3 day diary to list coughing and choking episodes and their association with meals. For each bout of coughing
they were asked to indicate severity using a four point scale: 1=minor, 2=cause breathlessness, 3=unable to breath for a time,
4=requires assistance or suction device. For each day that patients completed the diary, they were asked to indicate how distressing
any coughing and choking episodes had been using a six point scale the limits of which were “extremely distressing” and “no
problem”. A rough indication of the duration of each episode was also recorded.

Patients were asked to suspend recording during any period when they had an upper respiratory tract infection and to recommence
after full recovery. The capacity to volitionally cough was quantified by measuring peak cough flow5 and sound intensity. The peak cough flow (l/min) was measured by asking the patient to volitionally cough into a portable
electronic spirometer (MicroLab 3300). The sound intensity of volitional cough was measured by a sound level meter GA208.6 This is a portable, battery operated device that contains the appropriate electronics to convert the sound pressure into
a meter reading in decibels. Patients were asked to volitionally cough in front of the sound level meter's condenser microphone.

Clinical symptoms, smoking habit, affective state (using the hospital anxiety and depression scale7), oral secretions, and respiratory function (forced vital capacity (FVC)) were documented. Bulbar signs were measured using
a semiquantitative scale,8 and swallowing was assessed by a timed test of swallowing.9 This timed test provides a reliable and valid numerical measure of swallowing capacity (measured in ml/s) based on the time
taken to drink a known volume of water and expressed in relation to a normal range in age and sex matched subjects: the test
may be undertaken repeatedly at home or at the bedside in hospital: such a test provides quite different information from
videofluoroscopy.

Variables were assessed for distribution. Comparison of continuous variables between groups (of patients with MND) was made
using one way analysis of variance (ANOVA) or Kruskal-Wallis test. The χ2 test was used to test for independence of variables.

The study was approved by the Bro Taf local ethics committee in Cardiff. All patients and volunteers gave consent for the
study.

Results

Thirty seven successive patients with MND (25 men, mean age 66 (range 31–81) years and 12 women, mean age 69 (range 50–80)
years) and 23 healthy volunteers (13 men, mean age 51 (range 30–70) years and 10 women, mean age 57 (range 41–67) years) were
assessed. Only one of the patients with MND had chronic primary pulmonary disease (emphysema); he had a low sensitivity to
cough in relation to upper respiratory tract infections. He was taking salbutamol (5 mg four times daily) via an inhaler.
The clinical characteristics of the patients with MND are shown in table 1.

Two out of 23 healthy volunteers coughed over 3 days compared with 26 of 37 patients with MND (Kruskal-Wallis test, p<0.001,
table 2). The two healthy volunteers coughed briefly once or twice only. Of the patients with MND the number of episodes varied from
1–50 (table 2) and total duration of coughing from <2 minutes to 45 minutes over 3 days (table 2). Ten (27%) patients with MND described episodes as being moderately or very distressing, whereas 23 (73%) patients experienced
slight or no distress. Twelve (32%) patients recorded breathlessness (severity scale=2) or inability to breath (severity scale=3)
during the episodes. Eight (22%) patients recorded episodes of coughing or choking only during meals. Eighteen (49%) patients
had episodes of coughing or choking not associated with meals: of those, two did not record any episodes during meals over
3 days and nine (24%) recorded that sometimes they woke up at night coughing or choking.

Total number and duration (min) of coughing and choking episodes in 3 days

Patients with MND were divided into two groups based on the range of coughing and choking in healthy volunteers: those with
0–2 coughing episodes over 3 days (group 1) and those with >2 episodes (group 2, table 1). Patients within group 2 had a greater tendency to be women and to be older, to have an abnormal speech, a slower timed
test of swallowing, and a lower FVC% predicted than those patients within group 1 (table 1). Although smoking habit was not associated with number of episodes, smokers had significantly more severe (severity scale⩾2)
and prolonged (⩾1 minute) episodes of coughing and choking than non-smokers (χ2 test, p<0.05). Patients who had any upper motor neuron bulbar signs (brisk jaw jerk, spastic tongue movements, pseudobulbar
affect) had a greater tendency to have severe and prolonged episodes of coughing and choking (χ2 test, p<0.05).

Patients in group 2 (excess coughing/choking) tended to have a lower peak cough flow and cough intensity than those within
group 1, but this was only statistically significant for flow (table 3). Affective state and excessive oral secretions were not associated with the number, severity, or duration of episodes (table
1).

Only two of 26 patients with coughing and choking episodes had had a chest infection since the onset of MND symptoms (mean
duration 2.5 years): both were heavy smokers and one had diabetes, emphysema, and prostate carcinoma. None of the patients
who did not cough or choke reported any chest infections since the onset of MND symptoms.

Seven of 37 (19%) patients with MND died over 12 months of follow up. Six of seven of those patients reported coughing and
choking attacks during the 3 days of the assessment but there was no significant statistical association between having coughing
and choking episodes and death (χ2 test p>0.05): three of those patients described the episodes as moderate to very distressing, and prolonged (>1 minute).

Discussion

This is the first study to assess in detail the frequency and severity of coughing and choking episodes in patients with MND.
In healthy people a cough is a distinctive phenomenon and totally different from choking. However, many episodes described
by patients with MND are difficult to clarify and hence we have not attempted to distinguish them separately. Female sex,
older age, abnormal speech, slow timed test of swallowing, and low FVC% predicted were significantly associated with the group
of patients with MND who coughed more than the healthy volunteers over 3 days (>2 coughing episodes). A higher proportion
of female patients had abnormal speech and reduced swallowing consistent with the known higher frequency of a bulbar presentation
in elderly women and it is, therefore, unlikely that female sex and age are independent variables associated with coughing
and choking in MND.

The presence of any upper motor neuron bulbar signs was significantly associated with the severity and duration of coughing
and choking episodes. If spastic dysarthria and brisk palatal/pharyngeal reflexes are associated with the presence of excessively
brisk laryngeal closure reflexes then the reflexes may be triggered at a lower threshold than usual, and enhance the risk
of upper airway obstruction (feeling of choking). It might be expected that inefficient pharyngeal clearance with pooling
of saliva or detritus in the valleculae or pyriform fossae, and premature oral loss of food material could act as provocative
factors in triggering episodes: whether oesophageal reflux also contributes at night for instance is unclear. Furthermore,
bilateral bulbar involvement of upper motor neurons might impede the ability to suppress cough (analogous to laughing, crying,
or breathing with pseudobulbar palsy) leading to more frequent or protracted bouts once triggered.

Smokers tended to have more severe and prolonged attacks of coughing and choking than non-smokers. Smoking can cause airway
inflammation, and the release of specific inflammatory products (for example, bradykinin) may cause hyperactivity of the reflex
cough. Cessation of smoking may be useful in those patients with significant episodes of coughing and choking.

Patients with coughing and choking episodes had a tendency to have lower volitional respiratory and cough indices (FVC, peak
cough flow, and cough intensity) than those without. However, volitional control of respiration can be impaired by corticospinal
tract lesions,10 as may occur in MND, and therefore FVC measurements give an incomplete picture of respiratory function in these patients:
tests of non-volitional activation—for example, using CO2 rebreathing or reflex cough activation—might be used in principle. We have not used non-volitional respiratory tests in this
study. Similarly, the measurements of cough amplitude and intensity used in this study are based on volitional activation;
however, there is evidence that there are separate pathways for the volitional and reflex cough11 which could be selectively affected by MND. Coughing and choking episodes due to upper airway irritation might be more likely
to be initiated by the reflex cough than the volitional cough. An independent measure of cough intensity in response to reflex
cough triggering (analogous to stimulation of respiration by increased arterial CO2) would be of value. Selective involvement of pyramidal pathways to respiratory muscles and tongue can be demonstrated using
transcranial magnetic stimulation.12

Anxiety may exacerbate or trigger coughing and choking attacks in patients with MND, and sometimes anxiolytic agents (for
example, sublingual lorazepam) are prescribed to prevent or stop these episodes. However, this study showed that anxiety was
not specifically associated with the number, severity, or duration of episodes and in this context care is necessary in distinguishing
symptoms of anxiety due to acute hypoxia from those due to psychological causes.

Only two patients who recorded coughing and choking attacks had had an overt chest infection since the diagnosis of MND. However,
both of them were heavy smokers and one had other significant medical problems (diabetes, emphysema, prostate cancer) which
could have contributed to the pathogenesis of the chest infections. We have not systematically used any tests (for example,
videofluroscopy) to assess aspiration in those patients who coughed or choked. However, this study showed that, overall, coughing
and choking episodes are rarely associated with aspiration pneumonia. Whether, in this context, pneumonia is associated with
frequent minor or subclinical aspirations or larger single events or the aspiration of infected material is unclear. Recent
studies support the view that factors other than simple mechanical aspiration should be considered in the pathogenesis of
aspiration pneumonia (for example, oral/dental status, host resistance, pulmonary clearance, smoking).13

In conclusion, coughing and choking episodes are clinically underdiagnosed in MND; the results of the present study provide
information about the incidence and possible factors which are important in provoking these episodes. Upper motor neuron bulbar
involvement is likely to be an important factor in triggering cough (via dysphagia) and in reduced ability to suppress cough
once triggered. Reduction of exogenous stimuli likely to trigger laryngeal closure reflexes and medical suppression of such
brisk reflexes are potential avenues of treatment for these distressing symptoms.